Is ACTL9 p.Ser263Phe (c.788C>T) pathogenic?

ACTL9 p.Ser263Phe (c.788C>T) is classified Uncertain significance in ACTL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). Very rare (popmax 0.000424%, nfe).

How common is ACTL9 p.Ser263Phe (c.788C>T) in the general population?

ACTL9 p.Ser263Phe (c.788C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

ACTL9 p.Ser263Phe

c.788C>T · VCV3483961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.305	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -2.1, phastCons 0.65
Regional constraint	o/e 1.05	unconstrained · MANE · 1,247 bp · p 0.2 · regional, not allelic
Overall
CADD	18.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,998 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,356 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ACTL9
Protein: p.Ser263Phe
Coding: c.788C>T
MANE Select: NM_178525
Type: single nucleotide variant
Location: chr19:8697914 (GRCh38)
Gene constraint: LOEUF 1.575 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 87.56

Full ACTL9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTL9 p.Ser263Cys Uncertain significance ★ same residue
ACTL9 p.Ala174Asp Uncertain significance ★ same type
ACTL9 p.Ala174Thr Uncertain significance ★ same type
ACTL9 p.Ala187Ser Uncertain significance ★ same type
ACTL9 p.Ala319Ser Uncertain significance ★ same type
ACTL9 p.Ala361Thr Uncertain significance ★ same type
ACTL9 p.Ala388Asp Uncertain significance ★ same type
ACTL9 p.Ala392Gly Uncertain significance ★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/actl9-p-ser263phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown